Spherix Global Insights

September 15, 2022

Geographic Atrophy — A Look Into Clinical Development

Throughout my career in the ophthalmology field, I have come face to face with patients suffering from geographic atrophy (GA) and have witnessed firsthand the devastating impact it can have among those patients. I’ve grown passionate about educating others about the potential signs, symptoms, and consequences of GA, as well as the major risk factors associated with the disease, that I’ve gathered from the research I’ve conducted.

 

What is Geographic Atrophy?

Geographic atrophy is the advanced atrophic form of age-related macular degeneration, also known as AMD. It primarily causes impaired visual function and is the leading cause of impaired visual function among the elderly. The disease affects more than 5 million people worldwide, with 22% of affected persons being over 90 years old. Both GA and wet macular degeneration are always preceded by the dry form of AMD.

Symptoms include gradual loss of visual function, scotomas (large dark or blind spots in the visual field), difficulty recognizing faces, decreased reading speed, impaired dark adaptation, low luminance deficit (LLD), impaired contrast sensitivity, and difficulty driving at night. These symptoms occur as a result of lesions on the retina of the eye. When they do occur, GA lesions may not involve the center of the fovea until the very late stages of the disease. This means that while central vision may be preserved, areas of vision located just outside the point of fixation could be lost to scotomas (blind spots).

When it comes to the risk factors associated with GA, some are in our control while others are not. Genetics are one of the primary factors predicting the development of this condition, and family history becomes extremely relevant when assessing the likelihood of developing GA. Genes involved in the alternative complement cascade have consistently been implicated in AMD pathogenesis. Age is another primary risk factor, with those above the age of 85 being much more likely of developing the disease. This is why it is critical for patients in their later years to receive annual eye exams as to monitor any warning signs of the disease.

While you have no control over your age or family history, you do control smoking. – and to no surprise, Individuals who smoke cigarettes are also at a higher risk of developing GA. As far as demographics are concerned, Europeans are more likely to develop GA than other demographic groups, including Asians, Africans, and Hispanics.

 

How is GA diagnosed?

Since GA originates from AMD, we know that it has progressed to GA when well-defined patches of loss of the RPE (retinal pigment epithelium), photoreceptors, and choriocapillaris are observed using diagnostic images. In most cases, it is typical that physicians see GA start around the center of the macula, and as the lesions expand into the fovea, virtual function severely decreases. The macula is responsible for our central vision, allowing us to see the world in color and observe details around us. The fovea is the very center of the macula that allows for the sharpest visual acuity. When GA occurs, it creates lesions across our macula, therefore, any changes to it should be noted and closely monitored. Central vision loss can be a key indicator of disease progression.

A rather unfortunate fact is that GA makes up 10%-20% of all incidences of legal blindness caused by AMD. Legal blindness has a serious impact on a person’s ability to perform simple everyday tasks such as driving, reading, writing, cooking, socializing, and simply navigating around the house. Unfortunately, 42% of all patients suffering from GA are legally blind (20/200 or worse with best correction). Living with GA seriously impacts the quality of life for many patients and can also greatly reduce their independence.

One of the validated outcomes for GA progression is reading speed. Reading speed is inversely correlated with GA lesion size. Patients with advanced GA have great difficulty in reading due to the paracentral scotomas. Unfortunately, even patients who have 20/20 vision may still experience loss of reading function.

 

Clinical Development

There are currently no FDA-approved treatments for GA, however, there are many clinical studies taking place, including two agents in late-stage trials (one of which has filed for regulatory approval with the FDA.) Apellis Pharmaceuticals has conducted two Phase three trials, DERBY and OAKS, and has an ongoing extension study (the GALE trial) to evaluate the efficacy and safety of pegcetacoplan (APL-2) in patients with GA secondary to AMD. With data from both trials and a positive Phase two trial, Apellis has filed with the FDA and is expecting a regulatory decision by the end of November. If granted, pegcetacoplan would become the first FDA-approved therapy intended to slow the progression of GA.

Iveric Bio has also progressed to a pivotal phase three program (GATHER1 And GATHER2) and has released positive Phase three trial data showing their investigative agent, avacincaptad pegol, reduced the rate of GA lesion progression in both studies. If a positive trajectory continues for Iveric, the company plans to file with the FDA in the first quarter of next year.

While it is great news that two treatments have gotten so close to the finish line, there is still much work to do. GA is a slow progressing disease making clinical trial design challenging for treatments that not only slow GA progression, but also dry AMD progression. Ultimately, drug developers want to slow the natural progression of the disease and hopefully even stop progression before vision loss occurs.

While there are many other therapies in earlier stages of development, there still remains a drastic unmet need in geographic atrophy.

GA provides a life full of struggles and hardships for those that it affects. Impacting millions of people across the world, it is my hope that treatments become available for GA and that more steps are taken towards continuing to learn more about the disease process and natural history. For a disease that has such a wide reach, it is surprising to me how many people have never heard of it or seem to know very little about it. It will be interesting to see how the treatment landscape for GA evolves over the coming years to give hope to patients around the world.

To learn more about Spherix’s GA coverage click here.